Capsular polysaccharides galactoxylomannan and glucuronoxylomannan from Cryptococcus neoformans induce macrophage apoptosis mediated by Fas ligand

Abstract

SummaryThe effects of capsular polysaccharides, galactoxylomannan (GalXM) and glucuronoxylomannan (GXM), from acapsular (GXM negative) and encapsulate strains of Cryptococcus neoformans were investigated in RAW 264.7 and peritoneal macrophages. Here, we demonstrate that GalXM and GXM induced different cytokines profiles in RAW 264.7 macrophages. GalXM induced production of TNF-a, NO and iNOS expression, while GXM predominantly induced TGF-b secretion. Both GalXM and GXM induced early morphological changes identified as autophagy and late macrophages apoptosis mediated by Fas/FasL interaction, a previously unidentified mechanism of virulence. GalXM was more potent than GXM at induction of Fas/FasL expression and apoptosis on macrophages in vitro and in vivo. These findings uncover a mechanism by which capsular polysaccharides from C. neoformans might compromise host immune responses.

A Microbial Polysaccharide Reduces the Severity of Rheumatoid Arthritis by Influencing Th17 Differentiation and Proinflammatory Cytokines Production

“…Mouse Th17 differentiation occurs only in the simultaneous presence of IL-6 and TGF-␤, while IL-23 represents a growth factor rather than a differentiation factor (8). It has been previously reported that GXM is able to induce TGF-␤ in macrophages (49). In our experimental system GXM suppresses TGF-␤ in joints early after the onset of treatment.…”

“…This apparent discrepancy could be due to the different experimental systems used. In particular in a report from Villena et al (49) the regulation of GXM was evidenced in an in vitro system by using a macrophage cell line. This experimental condition is quite different from that used by us.…”

The Facultative Intracellular Pathogen Candida glabrata Subverts Macrophage Cytokine Production and Phagolysosome Maturation

“…72) and also for fungal pathogens such as Cr. neoformans (24). However, we did not observe signs of apoptosis by C. glabratainfected MDMs, indicating that, at least during the early stages (24 h) of interaction, C. glabrata does not induce apoptosis.…”

“…Additionally, C. albicans modulates the immune response indirectly via manipulating the host's cytokine response (22,23). The capsule of Cryptococcus neoformans has been shown to mediate macrophage apoptosis and therefore induces a distinct anti-inflammatory mechanism to kill the phagocyte (24). Cr.…”

Unusual Galactofuranose Modification of a Capsule Polysaccharide in the Pathogenic Yeast Cryptococcus neoformans

“…GXM is the more abundant capsule component; cells without it are acapsular and are avirulent in animal models of cryptococcal infection (28). GXMGal comprises less of the capsule mass but also exhibits potent immunomodulatory properties (32)(33)(34)(35)(36) and may regulate capsule expansion (37).…”